The prevalence of recalcitrant skin wounds resulting from the prosthetic device-skin interface ranges between 15% and 25%. Treatment options for these patients are limited. Repeat reconstructive surgical procedures are often necessary and thus auto-and allograft procedures are problematic. Since continued use of the prosthetic device is a necessity for these patients, a suitable exogenous material that could fill subcutaneous spaces, promote vascularization in ischemic tissues, and serve as a skin covering would be of significant benefit. This application is in response to RFA #HD 93-012 in which the stated objectives include identification of methods to improve wound healing, prevent secondary complications, and deliver growth factors to skin wound sites that will benefit this patient population. We have identified a biomaterial derived from the small intestinal submucosa (SIS) that has the ability to stimulate or induce host tissue to proliferate, remodel and even regenerate into a type of connective tissue that is appropriate for the particular location in the body that the material is placed. SIS supports epithelial growth, neovascularization and infection resistance. The implanted SIS is resorbed within 60 to 90 days leaving no material against which the host can mount an inflammatory response. We propose to optimize these properties for the local treatment of skin wounds caused by prosthetic devices. Two animals models will bemused, the rat and the Yucatan pig, in which chronic skin wounds with a granulation tissue bed will created over bony prominences. Various forms of xenogeneic SIS will be used to treat these wounds, including SIS with attached growth factors EGF, FGF, & PDGF. Measured variables will include wound contraction, vascularization, epithelialization, infection resistance, and mechanical properties of the remodelled tissue. We will also conduct studies to characterize the composition of the biomaterial, identify potential cytokines that may exist within the material, optimize in-vitro cell growth upon and within the material, and evaluate the immunologic response of this collagen based biomaterial. This work is divided into 4 integrated studies research team that will maintain a very focused, task oriented approach to the treatment of wounds created by the integument-device interface.